P-19

Frontotemporal dementia and neuronal ceroid lipofuscinosis

Ana Luísa Carvalho^I; Lina Ramos^I; Maria Margarida Venâncio^II; Isabel Santana^III; Carmo Macário^IV; Rosário Almeida^V; Jorge Saraiva^VI

^IMedical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
^IIMedical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal and Department of Medical Genetics, Faculty of Medicine, University of Coimbra, Portugal
^IIIDepartment of Neurology, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal and Faculty of Medicine, University of Coimbra, Portugal ]]> ^IVDepartment of Neurology, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
^VCNC, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal
^VIMedical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal and University Clinic of Pediatrics, Faculty of Medicine, University of Coimbra, Portugal

aluisa.dcarvalho@gmail.com

Introduction: Frontotemporal dementia is the second most frequent form of early-onset dementia. Its molecular basis is heterogeneous. Heterozygous mutation in the progranulin gene (GRN) is a frequent cause of this disease, with autossomal dominant inheritance. Recently, Smith et al. presented two brothers with adult-onset neuronal ceroid lipofuscinosis and homozygous mutation in the GRN gene (c.813_816del (p.Thr272Serfs*10)). This type of neuronal ceroid lipofuscinosis was designated type 11 (CLN11).

Case report: We report one family with frontotemporal dementia with molecular diagnosis: heterozygous for g.22632264dupGT (p.Ser301Cysfs*60) mutation in  the GRN gene. One member of this family presented with progressive visual failure at 25 years, followed by dystonia with muscle weakness, multifocal myoclonus and dysarthria. Plasma progranulin values are undetectable. The molecular analysis of GRN gene revealed a homozygous mutation g.22632264dupGT (p.Ser301Cysfs*60) confirming the diagnosis of CLN11.

Comment: Mutations in specific genes usually determine important phenotypes in either the heterozygous or homozygous state. In this two families, with mutations in the GRN gene, two clinical distinct neurological disorders are present: frontotemporal dementia at heterozygous    and    CLN11     at     homozygous     state. A deletion was present in Smith et al. previously reported family. The family reported by the authors is the first with homozygous state for a duplication in the GRN gene.